Glycosylphosphatidylinositol Anchors of Plasmodium falciparum: Molecular Characterization and Naturally Elicited Antibody Response That May Provide Immunity to Malaria Pathogenesis

doi:10.1084/jem.192.11.1563

Published online 27 November 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1563/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1563-1576

Original Article

Glycosylphosphatidylinositol Anchors of Plasmodium falciparum: Molecular Characterization and Naturally Elicited Antibody Response That May Provide Immunity to Malaria Pathogenesis

Ramachandra S. Naik^a, OraLee H. Branch^b, Amina S. Woods^c, Matam Vijaykumar^a, Douglas J. Perkins^b, Bernard L. Nahlen^b,e, Altaf A. Lal^b, Robert J. Cotter^c, Catherine E. Costello^f, Christian F. Ockenhouse^d, Eugene A. Davidson^a, and D. Channe Gowda^a
^a Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007
^b Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341
^c Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
^d Walter Reed Army Institute of Research, Silver Spring, Maryland 20910
^e Vector Biology and Control Center, Kenya Medical Research Institute, Kisumu, Kenya
^f Mass Spectrometry Resource, Boston University School of Medicine, Boston, Massachusetts 02118

Correspondence to: D. Channe Gowda, Department of Biochemistry and Molecular Biology, 3900 Reservoir Rd., N.W., Washington, DC 20007. Tel:202-687-3840 Fax:202-687-7186 E-mail:gowda{at}bc.georgetown.edu.

Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols(GPIs) of intraerythrocytic Plasmodium falciparum is believedto contribute to malaria pathogenesis. In this study, we purifiedthe GPIs of P. falciparum to homogeneity and determined theirstructures by biochemical degradations and mass spectrometry.The parasite GPIs differ from those of the host in that theycontain palmitic (major) and myristic (minor) acids at C-2 ofinositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectively,and do not contain additional phosphoethanolamine substitutionin their core glycan structures. The purified parasite GPIscan induce tumor necrosis factor ${alpha}$ release from macrophages.We also report a new finding that adults who have resistanceto clinical malaria contain high levels of persistent anti-GPIantibodies, whereas susceptible children lack or have low levelsof short-lived antibody response. Individuals who were not exposedto the malaria parasite completely lack anti-GPI antibodies.Absence of a persistent anti-GPI antibody response correlatedwith malaria-specific anemia and fever, suggesting that anti-GPIantibodies provide protection against clinical malaria. Theantibodies are mainly directed against the acylated phosphoinositolportion of GPIs. These results are likely to be valuable instudies aimed at the evaluation of chemically defined structuresfor toxicity versus immunogenicity with implications for thedevelopment of GPI-based therapies or vaccines.

Key Words: malaria parasite, cytokine response, antigenicity, acquiredimmunity, pathogenesis

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